Leishmaniasis is a tropical parasitic infectious disease caused by protozoa of the genus Leishmania parasitizing macrophages of a host such as a human, and is propagated mainly via sand flies living in the desert. The WHO (World Health Organization) has designated leishmaniasis as one of the six major tropical diseases. Patients thereof in Africa, Middle and Near East, Latin America, and Asia account for most of the worldwide patients (approximately 12 million people/year), and approximately 350 million people are threatened by infection thereof. Many of the people live in developing countries, and are hardly able to afford expensive drugs.
In the current treatment of leishmaniasis, pentavalent antimony formulations, such as pentostam, are used as first-line drugs. However, pentavalent antimony formulations are expensive, and side-effects caused by high toxicity thereof are problematic. Further, the emergence of drug-resistant protozoa has been confirmed in India, which poses a new serious problem. In a case in which antimony formulations may not be effective, diamidine compounds such as an isethionate salt of pentamidine (4,4′-(pentamethylenedioxy)dibenzamidine) are used (see, for example, Japanese National-Phase Patent Publication (JP-A) No. 9-501653), and macrolide antibiotics such as an antifungal antibiotic amphotericin B are secondarily used against fungal infection or mucocutaneous leishmaniasis. However, the efficacy of these diamidine compounds and amphotericin B is not as high as pentavalent antimony formulations. Further, these drugs are expensive, and various side-effects thereof have been reported.
Other known therapeutic drugs for leishmaniasis include antiprotozoal drugs containing germacrane and guaiane sesquiterpenoid compounds that have been extracted, purified, and separated from an Asteraceae plant (Elephantopus mollis H.B.K.) (see, for example, Japanese Patent Application Laid-open (JP-A) No. 2001-226369), and therapeutic drugs for leishmaniasis of which the active ingredient is a glucopyranose terpenoid derivative (see, for example, JP-A No. 11-106394). However, these therapeutic drugs have the drawback of low drug efficacy.
In recent years, it has been disclosed that rhodacyanine dyes of a certain type exhibit a strong cell-proliferation inhibiting activity against leishmania protozoa although the cytotoxicity thereof against mammalian cells, which is an index of side-effects, is low, and the rhodacyanine dyes thus have a high selective toxicity coefficient, and are effective as anti-leishmania agents (JP-A Nos. 2004-331545 and 2006-104116). However, results thereof in a leishmania protozoa proliferation inhibiting test in macrophages, and activity thereof in an experimental system in which a pathological model of infected animals is used, have not been reported.